Comparative Study Of Liver Function And Regeneration By Different Hepatic Inflow Occlusion Methods After Hepatectomy In Rats With Liver Cirrhosis

Objective:At present, the focus of studies on different hepatic inflowblocking (DHIB) for hepatectomy is mostly on protection and treatment ofischemic reperfusion injury to liver, in order to enhance regeneration of residualliver. However, there were a few animal experimental researches of the impactsof DHIB on hepatocytes regeneration postoperatively, especially its effects inanimal with cirrhotic liver were unknown. In China, most patients withhepatocellular carcinoma (HCC) had a background of liver cirrhosis due to virushepatitis, therefore, an animal model of liver cirrhosis in rat was establishedfirstly in this study, on which a comparison study on liver function andregeneration by DHIB were carried out.Methods: A conventional technique of subcutaneous injection of CCl4andethanol was employed to create the model of rat liver cirrhosis. The proceduresfor hepatic inflow blocking were divided into4groups:1. Pringle maneuver（PR）;2.hemihepatic vascular block(HH);3.hepatic inflow block withouthalf-hepatic artery(WH);4.sham operation (SH).70%of the liver wasresected in group of1-3according to Higgins method. Samples of blood andliver tissue were collected at0h,1d,3d and7d postoperatively to exam hepaticenzymologic (ALT,AST,ALB) and histological changes, meanwhile rate ofresidual liver regeneration and expression of IL-6, CyclinD1and PCNA by RT-PCR and immuno-histological technique were recorded.Results:1. The mortality of creating an animal model was5.9%, andsuccessful rate for setting a liver cirrhosis was86.7%.2. Postoperative enzymechanges were similar in all groups, that was ALT and AST increased rapidlyafter hepatectomy (p<0.05compared with SH group) and reached the peak at1dthen decreased gradually. However, among the3operative groups, theparameters were higher in PR group at different points than in HH and WHgroups significantly (p<0.05). At7d, there were no differences between SHgroup and HH, WH groups (p>0.05). ALB levels were significantly lower in3operative groups than in SH group (p<0.05). After1d, its level increasedgradually and was higher in WH and HH groups than in PR group (p<0.05).3.Histological changes in PR group at1d were observed as follows: unclearlobular structure, edema hepatocytes with compressed sinusoid, hepatocytesnecrosis and infiltration of inflammatory cell and so on. However, thepathological lesions mentioned above were slighter in WH and slightest in HHgroups at the same time.4. The rates of liver regeneration in3operated groupswere slowed with lower peak values compared with SH group, but thesechanges were more obvious in PR group than the other two groups (p<0.05).5.The mRNA expressions of IL-6and CyclinD1were no different in4groupspostoperatively at0h. However, their expressions were higher in WH and HHgroups than in PR at1and3d (p<0.05), but no significance between WH andHH groups (p>0.05).6. The variation of labeling index of PCNA was similar tothat of IL-6mRNA and CyclinD1at the time points of1、3、7days after theoperation.Conclusion:1. The animal model established by us is satisfy for study andeasy to be performed with a high successful rate.2. On the part of effects on liver function and pathological changes, techniques of WH and HH were betterthan traditional one of PR in rats hepatectomy with liver cirrhosis.3. As regardsto liver regeneration after hepatectomy in rats with cirrhosis, WH and HHgroups showed similar results, which were better than that in PR group. Themechanism of this role is possibly related to early high expression of IL-6andCyclinD1mRNA, which may enhance regeneration of residual cirrhotic liver.